The overall objective is to identify and understand the factors which control the balance of energy derived from endogenous carbohydrate and lipids during sustained, submaximal exercise. The theoretical basis is the crossover concept that during rest and mild to moderate exercise in the fasted state, lipids provide the greatest proportion of energy. As the intensity increases from moderate to hard to maximal, even in the trained state the balance of substrate utilization switches from lipid to carbohydrate. The project will delineate mechanisms by which dietary history, exercise intensity, and training state affect the balance of substrate utilization. Also, because blood glucose and free fatty acid pools are limited in capacity compared with the fluxes sustained during exercise, regulation of these pools during exercise will be described. The aims of the project are (1) to describe the interactive effects of nutritional status, training status, and exercise intensity on gluconeogenesis during exercise; 2) evaluate the hypothesis that muscle mitochondrial uptake of fatty acids limits lipid oxidation during exercise, and 3) evaluate the effects of the menstrual cycle on the capacity to utilize lipid energy sources. To address these aims, men and women will be studied at rest and during exercise of given absolute and relative intensities, both before and after training. In women, the effects of menstrual cycle phase on the balance of substrate utilization will be determined. In men, endurance training, lactate, dichloroacetate, and heparin plus Intralipid infusion will be used to dissect where resistances exist in substrate supply during exercise. Indirect calorimetry, primed-continuous dual stable isotope infusion, isotope and isotopomer analyses, and glucoregulatory hormonal analyses will be used to address the specific aims.